与 (Pb) 诱导的嗅觉上皮质毒性相关的内质网膜应激,在嗅觉暗基底细胞系中
Bing Han1, Teru Kamogashira1, Shu Kikuta1,2
1Department of Otolaryngology and Head and Neck Surgery, Faculty of Medicine, University of Tokyo, Tokyo, Japan.
暴露于会通过内质网膜 (ER) 应激和亡来损害嗅觉细胞,而不是细胞亡. 在这些细胞中,HEPES缓冲器提供了对毒性的部分保护.
科学领域:
- 毒理学 毒理学 毒理学
- 细胞生物学 细胞生物学
- 神经科学是一个神经科学.
背景情况:
- (Pb) 是一种已知会导致器官损伤和神经发育问题的有毒物质.
- 嗅觉细胞对于嗅觉感知至关重要,并且可能容易受到环境毒素的影响.
- 了解诱导细胞死亡的机制对于公共健康至关重要.
研究的目的:
- 研究 (Pb) 毒性在嗅觉细胞中的特定机制.
- 确定内 плазма网膜 (ER) 应激,亡和亡在Pb诱导的嗅觉细胞损伤中的作用.
- 评估HEPES缓冲器对Pb毒性的潜在保护作用.
主要方法:
- 使用DBC1.2嗅觉细胞系进行实验性暴露 (Pb).
- 使用定量PCR分析了ER压力,亡和亡的关键分子标志物.
- 评估了细胞通路对不同度Pb的剂量依赖反应.
主要成果:
- 暴露显著增加了ER压力标志物的表达 (GRP94,GRP78,拼接XBP1,PERK,ATF6) 在剂量依赖的方式.
- 细胞亡标志物 (Caspase 3,Caspase 12) 没有显著增加,表明细胞亡不是细胞死亡的主要途径.
- 亡标志物 (RIPK3,MLKL) 的表达增加,证实了亡途径的激活.
- HEPES缓冲器显示了对Pb诱导的ER压力,亡和亡的部分保护作用.
结论:
- 暴露于会诱导嗅觉细胞的剂量依赖性细胞毒性,主要是通过ER压力和亡.
- 亡途径是嗅觉细胞中诱导毒性的关键调解者.
- HEPES缓冲剂可能提供一种保护策略,防止对嗅觉细胞的有害影响.
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